Heart disease is one of the major cause of death in the world. Identifying the molecular events during heart development will permit the advancement of preventing and treatment heart disease. This project will focus on elucidating the role of MEF2D during heart development with particular attention to the differentiation of muscle cells. MEF2D conditional null mice will be generated and used to exam the role of MEF2D in muscle development. Concurrently, MEF2D inactivated embryonic stem (ES) cells will be employed to study the role of MEF2D during cell differentiation in vitro. Using over expressed MEF2D ES cells, we will perform microarray analysis to identify MEF2D's downstream targets. Biochemical experiments will be performed on these newly identified genes to determine the transcriptional pathways that MEF2D regulates during heart development.